title: Hydrogen peroxide-responsive copolyoxalate nanoparticles for detection and therapy of ischemia-reperfusion injury.
abstract: The main culprit in the pathogenesis of ischemia/reperfusion (I/R) injury is the generation of high level of hydrogen peroxide (H2O2). In this study, we report a novel diagnostic and therapeutic strategy for I/R injury based on H2O2-activatable copolyoxalate nanoparticles using a murine model of hind limb I/R injury. The nanoparticles are composed of hydroxybenzyl alcohol (HBA)-incorporating copolyoxalate (HPOX) that, in the presence of H2O2, degrades completely into three known and safe compounds, cyclohexanedimethanol, HBA and CO2. HPOX effectively scavenges H2O2 in a dose-dependent manner and hydrolyzes to release HBA which exerts intrinsic antioxidant and anti-inflammatory activities both in vitro and in vivo models of hind limb I/R. HPOX nanoparticles loaded with fluorophore effectively and robustly image H2O2 generated in hind limb I/R injury, demonstrating their potential for bioimaging of H2O2-associated diseases. Furthermore, HPOX nanoparticles loaded with anti-apoptotic drug effectively release the drug payload after I/R injury, exhibiting their effectiveness for a targeted drug delivery system for I/R injury. We anticipate that multifunctional HPOX nanoparticles have great potential as H2O2 imaging agents, therapeutics and drug delivery systems for H2O2-associated diseases.
authors.affiliation: Department of BIN Fusion Technology, Chonbuk National University, Jeonju, Chonbuk 561-756, South Korea; Department of Polymer Nano Science and Technology, Chonbuk National University, Jeonju, Chonbuk 561-756, South Korea. Electronic address: dlee@jbnu.ac.kr.
authors.forename: Dongwon
authors.initials: D
authors.lastname: Lee
authors.forename: Soochan
authors.initials: S
authors.lastname: Bae
authors.forename: Qingen
authors.initials: Q
authors.lastname: Ke
authors.forename: Jiyoo
authors.initials: J
authors.lastname: Lee
authors.forename: Byungjoo
authors.initials: B
authors.lastname: Song
authors.forename: S Ananth
authors.initials: SA
authors.lastname: Karumanchi
authors.forename: Gilson
authors.initials: G
authors.lastname: Khang
authors.forename: Hak Soo
authors.initials: HS
authors.lastname: Choi
authors.forename: Peter M
authors.initials: PM
authors.lastname: Kang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D001592:Benzyl Alcohols / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D002460:Cell Line; D006861:Hydrogen Peroxide / Q000032:analysis / Q000378:metabolism*; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D061848:Optical Imaging; D019815:Oxalic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D015427:Reperfusion Injury / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000975:Antioxidants; D001592:Benzyl Alcohols; D011108:Polymers; C018966:4-hydroxybenzyl alcohol; D019815:Oxalic Acid; D006861:Hydrogen Peroxide
keywords: Bioimaging; Drug delivery; Hydrogen peroxide; Polymer; Theranostics